Scientists from the University of California San Diego have found an effective way to prevent the rejection of grafts derived from human embryonic stem cells by the human immune system.
The immune rejection of human embryonic stem cells is a major problem, limiting the development of human stem cell therapies.
Using a new humanised laboratory mouse, the scientists have now found that one combination of two immune suppressing molecules worked perfectly to protect cells derived from human embryonic stem cells from immune rejection.
Human embryonic stem cells have the capacity to differentiate several cell types, but the foreign cells are often rejected by the human immune system as they are different from our own body’s cells or ‘allogenic’.
According to the scientists, one way of overcoming the rejection problem is to give patients immunosuppressant drugs, which suppress the entire immune system.
UC San Diego professor of biology Yang Xu said: "For organ transplantation to save patients with terminal diseases that has been quite successful.
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"But for stem cell therapies, the long term use of toxic immunosuppressant drugs for patients who are being treated for chronic diseases like Parkinson’s disease or diabetes pose serious health problems."
Scientists have also been searching for a human immunity relevant model that will enable them to develop strategies to implant allogenic cells derived from embryonic stem cells safely.
"The problem is that we only had data from mouse immune system and those are not usually translatable in humans, because human and mouse immune systems are quite different," Xu added.
"So what we decided to do was to optimise the humanised mouse that carries a functional human immune system."
In order to do that, the scientists took immune deficient laboratory mice and grafted into their bodies human foetal thymus tissues and haematopoietic stem cells derived from fetal liver of the same human donor.
That reconstituted in these mice a normally functioning human immune system that effectively rejects cells derived human embryonic stem cells.
With the help of these ‘humanised’ mouse models, the scientists tested several immune suppressing molecules alone or in combination and discovered one combination that worked perfectly to protect cells derived from human embryonic stem cells from immune rejection.
Scientists discovered that the combination of CTLA4-lg, an FDA-approved drug for treating rheumatoid arthritis that suppresses T-cells responsible for immune rejection, and a protein called PD-L1 known to be important for inducing immune tolerance in tumours, allowed the allogeneic cells to survive in humanised mice without triggering an immune rejection.
This discovery could help resolve some of the major problems currently limiting the use of embryonic stem cells for certain conditions, paving the way for the development of more effective human stem cell therapies.
It might also provide scientists with a better understanding of how tumours evade the human immune system when they spread all over the body.